Impedance spectroscopy method for monitoring ischemic mucosal damage in hollow viscous organs

ABSTRACT

Alternate embodiments of an impedance spectroscopy method are disclosed for monitoring ischemic mucosal damage in hollow viscous organs. In each embodiment, a sensor catheter is placed inside a patient&#39;s hollow viscous organ. Afterwards, the catheter is electrically driven to obtain a complex impedance spectrum by causing two electrodes in the tip of the catheter to inject a current into the mucosal tissue at different frequencies, while two other electrodes measure the resulting voltages. A pattern recognition system is then used to analyze the complex impedance spectrum and to quantify the severity of the mucosal injury. Alternatively, the complex impedance spectrum can be appropriately plotted against the spectrum of normal tissue, allowing for a visual comparison by trained personnel.

This application is a divisional application of a pending Utility patentapplication Ser. No. 09/907,781, filed Jul. 18, 2001, which claimspriority from a Provisional Patent Application Ser. No. 60/219,281 filedJul. 19, 2000.

FIELD OF THE INVENTION

The present invention relates to systems and internal sensors formonitoring and quantifying ischemic damage in tissues.

BACKGROUND OF THE INVENTION

The gastrointestinal mucosa is at great risk of ischemia in thecritically ill, and its disruption has been shown to be the motor ofmultiple organ failure, a leading cause of death. Knowledge of the levelof damage can help guide therapy, reversing moderate damage and/orpreventing further complications. For example, as indicated by path A inFIG. 6, the status of a healthy person's mucosa changes little, if atall, over time. Path C shows how the damage level of an ill person'sischemic mucosa greatly increases over the course of several hours ifunchecked. However, as shown by path B, further damage can be arrestedif the ischemic damage is detected and an appropriate course oftreatment is undertaken. Unfortunately, there exists no clinicallysuitable method to directly monitor ischemic mucosal damage in thegastrointestinal tract of the critically ill patient.

Impedance spectroscopy has been used to detect ischemia (a condition ofinadequate blood flow and oxygen delivery to a given tissue) inbiological tissues using different instrumental methods. Impedancespectroscopy differs from other impedance measurements (which have longbeen used for a variety of biomedical applications such as cardiacoutput estimation, body fat measurement, and plethismography) in that itinvolves multiple measurements over a range of frequencies that as awhole contain significantly more information of the structural andelectrical properties of the sample. For example, U.S. Pat. No.5,454,377 to Dzwoczyk et al. teaches the assessment of ischemia in themyocardium, U.S. Pat. No. 5,807,272 to Kun et al. teaches the assessmentof ischemia in directly accessible tissues (surface or subjacenttissue), and U.S. Pat. No. 6,055,452 to Pearlman shows the generalcharacterization of the status and properties of tissues. However, noneof these references show or describe a clinically acceptable method forimpedance spectroscopy measurements of the inner wall of hollow viscousorgans such as the gastrointestinal mucosa, in vivo or in situ.

On the other hand, several other methods have been devised to detectand/or monitor gastrointestinal ischemia using different measurementtechnologies. These include tonometry (as shown in U.S. Pat. Nos.5,788,631 and 6,010,453 to Fiddian-Green), direct in situ measurementusing an electrochemical sensor (as shown in U.S. Pat. No. 5,158,083 toSacristán), and direct in situ measurement using an optochemical sensor(as shown in U.S. Pat. No. 5,423,320 to Salzman et al.) Additionally,U.S. Pat. No. 5,771,894 to Richards et al. shows external, non-invasivemeasurement using a magnetometer.

Numerous gastrointestinal catheter combinations, using electrodes orother sensors, have been used over the years for various measurementsand medical applications. For example, U.S. Pat. No. 5,657,759 toEssen-Moller discloses a gastrointestinal output catheter, U.S. Pat.Nos. 5,848,965 and 5,438,985, both to Essen-Moller, show a gastric pHsensor/catheter combination, and U.S. Pat. No. 5,477,854 to Essen-Mollerdiscloses a helicobater pylori gastric infection sensor. Furthermore,U.S. Pat. No. 5,833,625 to Essen-Moller shows a gastric reflux monitor,U.S. Pat. No. 6,010,453 to Fiddian-Green shows a pressure nasogastricsump and tonometer combination, U.S. Pat. No. 5,158,083 to Sacristán etal. discloses a miniature pCO₂ probe and catheter, and U.S. Pat. No.5,423,320 to Salzman et al. shows an air tonometry sensor and catheter.

Several therapies have been proposed to limit or reverse thegastrointestinal mucosal damage and/or the associated complications incritical patients, including, for example, aggressive hemodynamicresuscitation (as shown in Gutierrez et al.), NO synthase modulators (asshown in U.S. Pat. No. 5,585,402 to Moncada et al.), rBPI protein (asshown in U.S. Pat. No. 6,017,881 to Ammons et al.), oral glutamine (asshown in U.S. Pat. No. 5,981,590 to Panigrahi et al.), and DHEA (asshown in U.S. Pat. No. 5,922,701 to Araneo). All of these can beoptimally effective if they are administered within ideal treatment timewindows depending on the status of the mucosa.

Accordingly, it is a primary object of the present invention to providea unique method not only for detecting ischemia, but also for monitoringand quantifying ischemic mucosal damage, that is of great clinical valueas a therapeutic guide for patients with intestinal ischemia and/orshock.

Another primary object of the present invention is to provide such amethod that uses impedance spectroscopy with a sensor catheter insidehollow viscous organs.

Yet another primary object of the present invention is to provide such amethod that uses an impedance spectroscopy system, and a sensorcatheter, to monitor the level of damage of the gastric mucosa incritically ill patients.

SUMMARY OF THE INVENTION

A method is disclosed that uses impedance spectroscopy to monitorischemic mucosal damage in a hollow viscous organ. In the preferredembodiment, the preferred method comprises: electrically driving asensor catheter, inside a hollow viscous organ, to obtain a compleximpedance spectrum of tissue proximate the catheter; and using thecomplex impedance spectrum to determine the extent to which the tissueis damaged, as opposed to just determining if the tissue is ischemic.More specifically, as mentioned above, ischemia is a condition ofinadequate blood flow and oxygen delivery to a given tissue, which mayor may not result in tissue damage (i.e., ischemic tissue can beundamaged, and vice versa). Thus, detecting tissue ischemia does notresult in a measurement of tissue damage, and a different process, asimplemented in the present invention, must be utilized to do so.

The preferred catheter, which is configured to be inserted into anyhollow viscous organ, comprises four Ag/AgCl electrodes positioned on anend tip of the catheter. The electrodes are functionally ring-shaped,and are coaxially spaced apart a short distance from one another. Theouter two ring electrodes inject current into the tissue, and the innertwo electrodes measure the resulting voltage. Leads, electricallyconnected to the electrodes, extend along the wall of the cathetertubing or in a lumen portion of the tubing, and terminate at aninterface plug suitable for connection to the impedance spectrometer.Once the catheter is in place in one of a patient's hollow viscousorgans, the impedance spectrometer causes the electrodes in the tip ofthe catheter to inject a current into the mucosal tissue at differentfrequencies, allowing for the measurement of the tissue's compleximpedance spectrum. The spectrum contains information of the structuraland metabolic status of the tissue, and can be used to quantify thelevel of damage. More specifically, the spectrum can be appropriatelygraphically plotted against the spectrum of normal tissue, allowing fora direct visual comparison by trained personnel, and, therefore, anindication or measurement of damage. Alternatively, a standard patternrecognition system or the like may be used to automatically analyze thecomplex impedance spectrum and quantify the severity of the mucosalinjury.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects, and advantages of the presentinvention will become better understood with respect to the followingdescription, appended claims, and accompanying drawings, in which:

FIG. 1 is a schematic view of an impedance spectroscopy system formonitoring ischemic mucosal damage in hollow viscous organs;

FIG. 2A is a cross-sectional elevation view of a catheter for use withthe impedance spectroscopy system;

FIG. 2B is a perspective view of an electrode portion of the catheter;

FIG. 2C is a cross-sectional plan view of an alternative upper portionof the catheter;

FIG. 3 is a cross-sectional elevation view of a second embodiment of thecatheter;

FIG. 4A is an exploded view of a third embodiment of the catheter;

FIG. 4B is an elevation view, partly in cross-section, of a portion ofthe catheter shown in FIG. 4A, once assembled;

FIG. 4C is a detail view of a portion of FIG. 4A;

FIGS. 5A-5C are perspective views of a fourth embodiment of thecatheter;

FIG. 6 is a diagrammatic graph showing mucosal structure (e.g., aslining an intestinal wall) and different courses of mucosal ischemicpathogenesis;

FIG. 7 is a schematic illustration of the operation of the catheter; and

FIGS. 8A-11C are various graphs or plots illustrating how ischemicmucosal damage in hollow viscous organs is detected and/or quantifiedaccording to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

This application concerns a method referred to in non-elected claims ofthe “parent” Utility patent application Ser. No. 09/907,781, filed Jul.18, 2001.

Turning now to FIGS. 1-11C, preferred embodiments of a unique methodthat use an impedance spectroscopy system 10, with catheters 12 a-12 d,for monitoring ischemic mucosal damage monitoring in hollow viscousorgans, will now be given. The catheters 12 a-12 d are generallysimilar, in that each one has two or four electrodes with annular sidesurfaces positioned at a distal end of the catheter. For example, thecatheter 12 a comprises a flexible tube 14 and two or four generallycylindrical electrodes 16 a-16 d disposed at one end thereof. Theelectrodes 16 a-16 d are electrically connected, via leads 18 a-18 dextending up through the tube 14, to an impedance spectrometer 20portion of the system 10. The spectrometer 20 is used in conjunctionwith a signal processing device 22, such as an appropriately-programmedgeneral purpose computer, for processing the complex impedance spectrumto detect tissue damage. To monitor mucosal damage, the catheter isplaced in one of a patient's hollow viscous organs 24, and current isinjected by two of the electrodes 16 a, 16 d at a range of frequencies.The other two electrodes 16 b, 16 c measure the resulting voltagespectrum, which is subsequently processed and analyzed by thespectrometer 20 and signal processing device 22.

FIGS. 2A-2C show a first embodiment 12 a of the preferred catheter, usedin the preferred method. The catheter 12 a comprises the flexibleplastic tube 14 that can be inserted in any hollow viscous organ (e.g.,14-16 french). At the distal end or tip of the tube 14 are located thetwo or four electrodes 16 a-16 d (i.e., the catheter can be providedwith either two electrodes or four electrodes) that function asionic-current-to-electronic-current transducers, such as Ag/AgClelectrodes. The electrodes are substantially identical. As best shown inFIG. 2B, each has a cylindrical central portion (e.g., 24 a) having afirst diameter and two annular side surfaces (e.g., 25 a, 25 b), and twocylindrical extensions (e.g., 26 a, 26 b) attached to the ends of thecentral portion and coaxial therewith. Each extension (e.g., 26 a, 26 b)has a second, reduced diameter, and each electrode 16 a-16 d has anaxial through-bore.

The electrodes 16 a-16 d are spaced equally apart from one another alongthe distal tip of the catheter 12 a, and are separated by spacers (shortlengths of tubing) 27 a-27 d. As best seen in FIG. 2A, the annular sidewalls of the central portions 24 of the electrodes 16 a-16 d are theonly portions thereof that are exposed to the outside of the catheter 12a. Thus, each electrode 16 a-16 d is ring-like in functionality, and thedistal end of the catheter (with the electrodes) is generally radiallysymmetric. The catheter, therefore, will provide the same measurementsregardless of its radial orientation in an organ.

The diameters of the central electrode portions (e.g., 24 a) are aboutthe same as the outer diameter of the tube 14. This ensures that theouter surface of the catheter 12 a is relatively smooth, e.g., that ithas no more than minor surface roughness or undulations. The electrodes16 a-16 d are respectively electrically connected to the leads 18 a-18 d(via soldering, welding, or the like) in the electrodes' axialthrough-bores. The leads from the distal three electrodes 16 b-16 dextend through the axial through-bores of the other electrodes, asapplicable. The electrodes 16 a-16 d, leads 18 a-18 d, and shortportions of tubing are kept in place and stabilized via an epoxy orplastic fill 28.

The catheter 12 a may be a stand alone sensor catheter, or it may beprovided as part of a feeding/sump tube or some other type of lifesupport tube or catheter. For example, as shown in FIG. 2A, the catheter12 a doubles as a feeding tube. More specifically, the end of thecatheter 12 a is provided with the electrodes 16 a-16 d, while theremainder of the tube 14 is left hollow to act as a feeding line 29.Additionally, the catheter tube 14 may include a second lumen forsampling and feeding, like a Levin type gastric catheter, and/or a thirdlumen for a vented feeding/sump tube, as in a Salem type gastriccatheter. For example, as shown in FIG. 2C, the electrical leads 18 a-18d extend down through a side wall portion of the tube 14 having a ventlumen 30 and a feeding/sump lumen 32.

To manufacture the catheter 12 a, the leads 18 a-18 d are fed throughthe tube 14, if needed (since the leads may be provided as part of thetube 14 during the tube's manufacturing process), and through theelectrode through-bores, as applicable. The leads are subsequentlyelectrically connected to the respective electrodes. Then, the proximateelectrode 16 a is inserted in the end of the tube 14, one of the shortlengths of tubing is affixed to the proximate electrode 16 a, and so on.Adhesive may be used to hold the components together in this manner.Finally, the plastic or epoxy fill 28 is injected into the space betweenthe tubing portions, electrodes, and partially into the tube 14, and isallowed to set. The end of the fill 28 is rounded, as shown in FIG. 2A,to ease insertion of the catheter into a patient. As will be appreciatedby those of skill in the manufacturing arts, the catheter 12 a can bemanufactured according to a number of different methods and/or steps.For example, the catheter could be extruded from a machine.

If the catheter 12 a is provided with four electrodes, the two outerring electrodes 16 a, 16 d inject a current into the tissue, and the twoinner electrodes 16 b, 16 c measure the resulting voltage, as shownschematically in FIG. 7. In the two electrode configuration (not shown),the electrodes are used for both current source and voltage measurement.As mentioned above, the electrodes 16 a-16 d are respectively connectedto the leads 18 a-18 d that provide an electrical connection to theother end of the catheter along the wall of the tubing or in the lumen.At the other, proximal end of the catheter, the leads 18 a-18 d end inan electrical multi-channel connector 34 that can be plugged into theimpedance spectrometer 20.

FIG. 3 shows a second, alternative embodiment of the catheter 12 b.Here, the catheter 12 b has four tubular or ring-like electrodes 36 a-36d simply placed over (and adhered to) the exterior surface of the tubing14, with the leads extending from the electrodes down through the tubewall. In this case, the electrodes would have to be as thin as possibleto minimize surface roughness.

FIGS. 4A-4C show a third embodiment of the catheter 12 c. The catheter12 c is generally similar to the catheter 12 a, but has spacers (e.g.,42 a, 42 b, 42 c), provided with annular internal sockets or spacer lips(e.g., 52 a, 52 b), into which flanged electrodes (e.g., 44 a, 44 b)lock into place. In this sample interlocking means, each flangedelectrode (e.g., 44 a, 44 b) has a cylindrical central portion (e.g., 46a, 46 b) having a first diameter and two annular side surfaces, twoextensions (e.g., 48 a, 48 b) attached to the ends of the centralportion and coaxial therewith, and an axial through-bore. The extensions(e.g., 48 a, 48 b) each have a second, reduced diameter, but instead ofbeing purely cylindrical, the extensions (e.g., 48 a, 48 b) have annularelectrode lips (e.g., 50 a, 51 a) that face towards the central portion46. Additionally, the spacers (e.g., 42 a-42 c) are made of flexibleplastic tubing (i.e., a relative non-conductor of electricity) or thelike. Each spacer has two annular, inwardly-facing shoulders, in thisembodiment, which form the sockets (e.g., 52 a, 52 b). The shoulders arespaced back a bit from the open ends of the spacers. As shown in FIG.4B, the electrode extensions (e.g., 48 a, 48 b) are dimensioned to fitwithin the spacers (e.g., 42 a, 42 b), such that the electrode lips(e.g., 50 a, 50 b) abut the shoulders, locking the flanged electrodes(e.g., 44 a, 44 b) to the spacers (e.g., 42 a-42 c).

The catheter 12 c is assembled similarly to the catheter 12 a, asdescribed above. More specifically, the leads are electrically connectedto the electrodes (e.g. 44 a, 44 b) and are threaded through the spacersand electrodes, and the electrodes (e.g., 44 a, 44 b) are locked intosuccessive spacers (e.g., 42 a, 42 b) to form an assembly of two or fourelectrodes. As should be appreciated, since the electrodes (e.g., 44 a,44 b) simply snap into the spacers (e.g., 42 a, 42 b), assembly is muchquicker. Finally, the assembly is filled with the epoxy or plastic fill28 to further hold the assembly together and to provide a rounded tip,e.g., as shown in FIG. 2A. Also, the ends of the leads are connected tothe multi-channel connector 34.

To give the catheter 12 c a smooth, low-friction outer surface, thediameter of the central portions (e.g., 46 c) of the electrodes (e.g.,44 a) may be initially slightly greater than the outer diameter of thespacers (e.g., 42 a, 42 b), as shown in FIG. 4C. Then, once the catheter12 c is assembled, the outer surface of the catheter is sanded, removethe portions (e.g., 54) of the electrodes that extend past the spacers.

FIGS. 5A-5C show a fourth embodiment of the catheter 12 d. The catheter12 d comprises: an injection-molded, plastic tip 60; two or fourelectrodes 62 a-62 d; one or three spacers 64 a-64 c (i.e., in the caseof two electrodes, one spacer is needed, while three spacers are neededfor a four electrode catheter); dual-lumen tubing 66 or the like; andthe cables or leads 18 a-18 d. As best shown in FIG. 5B, the plastic tip60 comprises a rounded fore portion 68 and a rounded, trough-likeprojection 70 that extends back from the fore portion 68. As indicated,the tip 60 can be injection molded, or it can be made via anothersuitable manufacturing process. The electrodes 62 a-62 d and spacers 64a-64 c are generally similar in shape. Each has a small, cylindricalpassageway (e.g., 72 a, 72 b, 72 c, 72 d) for the cables 18 a-18 d, aswell as a rounded through-bore (e.g., 74 a, 74 b, 74 c, 74 d) throughwhich the trough-like projection 70 of the tip 60 is dimensioned to fit(i.e., the rounded through-bores, e.g., 74 a, 74 b, 74 c, 74 d, andprojection 70 are complementary in shape). Additionally, the outerdiameters of the electrodes and spacers are the same as the outerdiameter of the tip 60, which has the same outer diameter as the tubing66. To assemble the catheter 12 d, the cables 18 a-18 d are respectivelyelectrically connected to the electrodes 62 a-62 d, and alternatingelectrodes 62 a-62 d and spacers 64 a-64 c are slid over the projection70. Simultaneously, the cables 18 a-18 d are inserted through thepassageways (e.g., 72 a, 72 b, 72 c, 72 d), as applicable. Then, theportion of the projection 70 not covered by electrodes and spacers isslid into the tubing 66, as shown in FIG. 5A. Appropriate fasteningmeans, such as a solvent or an adhesive, are used to hold the componentsof the catheter 12 d together.

As should be appreciated, the rounded through-bores 74 and projection 70can be provided in any of a number of complementary shapes. For example,the projection and through-bores can be V-shaped, square, or circular.However, having a V- or trough-shaped projection, or a projection withanother shape where the electrodes and spacers have to be oriented in aparticular manner to be positioned over the projection, facilitatesassembly and enhances structural stability.

Referring back to FIG. 1, the system 10 generally consists of threeelements: any of the catheters 12 a-12 d; the impedance spectrometer 20;and the signal processing device 22. The impedance spectrometer 20 is anelectronic instrument that includes electrical patient isolation and canmeasure the impedance spectrum of the mucosa in the range of 10 Hz (orthereabouts) to 10 MHz (or thereabouts). The spectrum may be obtained bya frequency sweep from a synthesizer or by a pulse, and processed bysuch methods as synchronous demodulation or Fast Fourier Transform, orany other similar method. The output of the spectrometer 20 is thecomplex impedance spectrum measured in digital form. Spectrometers andprocessing methods suitable for adaptation for use in the presentinvention are well known to those of skill in the art, for example, asshown in U.S. Pat. No. 5,807,272 to Kun et al., U.S. Pat. No. 5,633,801to Bottman, and U.S. Pat. No. 5,454,377 to Dzwonczyk et al. Theentireties of these patents are hereby incorporated by reference.

Once the complex impedance spectrum is obtained, the results areprocessed by the signal processing device 22. The signal processingdevice 22 may be an appropriately-programmed general purpose computer,or a dedicated analog and/or digital device, both of which are wellknown to those of ordinary skill in the art. For processing the compleximpedance spectrum obtained by the spectrometer 20, the signalprocessing device 22 may graph or plot the spectrum for visual analysis,as discussed in further detail below. Alternatively, the signalprocessing device 22 may utilize a pattern recognition algorithm orsystem (e.g., running as software) or the like for analyzing the compleximpedance spectrum itself. The pattern recognition system uses apreviously trained or calibrated algorithm to classify the impedancespectrum measured and provided by the spectrometer 20. The output ofthis system is a numerical score (or other reference point) in anischemic damage index scale 80 validated experimentally via MRI's,chemical analysis, biopsy samples, or the like. In other words, thesignal processing device 22, implementing the pattern recognitionsystem, analyzes the impedance spectrum to determine to what extent theimpedance spectrum of the analyzed tissue deviates from that of normaltissue. The degree and character of deviation provides an actual measureof tissue damage, which translates into the ischemic damage index scale80, as validated experimentally (e.g., heavily damaged tissue, asdetermined experimentally, will have a certain pattern, and slightlydamaged tissue, as also determined experimentally, will have a differentpattern).

More specifically, as discussed above, the impedance spectrum of theanalyzed tissue is obtained by making multiple complex impedancemeasurements at different frequencies over the range of interest. Ateach frequency, an amplitude, Z, and a phase, φ, of the tissue responseare obtained. These values are then plotted as a function of frequency,or combined and plotted in the complex plane (resistance vs. reactance)in a Nyquist or a Cole-Cole plot (this latter term applies specificallyto tissue impedance spectra plots), where resistance (R) and reactance(X) are defined as:R=Z cos φ  Eq. 1X=Z sin φ  Eq. 2Analysis of these plots shows that normal tissue spectra have acharacteristic shape or pattern. According to the Cole-Cole electricmodel of biological tissues, this shape is the arc of a circle whenplotted in the complex plane. However, if tissue is damaged after anextended period of ischemia, the spectra of the damaged tissue losesthis characteristic shape. In fact, when plotted in the complex plane,the spectra of the damaged tissue become sigmoid- or S-shaped, deviatingsignificantly from the normal tissue spectra.

FIGS. 8A-11C show averaged experimental data obtained in the smallintestine of a group of test subjects subjected to a period ofintestinal ischemia followed by a period of reperfusion (restored bloodflow), in comparison to a group of test subjects in which normalperfusion and oxygenation was maintained. The data is presented in boththe frequency plots and in the complex plane. For the Nyquist plots(complex plane), the data has been normalized so that the shapes of thecurves can be more easily compared, e.g., the point at the highestmeasurement frequency (300 KHz) has a dimensional impedance of 1 and aphase angle of 0.

FIGS. 8A-8C show the impedance spectra of intestine with less than tenminutes of reduced blood flow, wherein the intestine is alreadyischemic, with associated rising acidity. In particular, FIGS. 8A and 8Bshow the average amplitude and phase impedance spectra, respectively, ofboth normal intestine and the intestine subjected to reduced blood flow,while FIG. 8C shows the normalized Nyquist plot of the normal andischemic intestinal tissue. As can be seen, although the intestine withreduced blood flow is ischemic, the tissue is not yet damaged, and thespectra are not easily distinguishable from the spectra of the normallyperfused intestines. Note that the spectra contain some noise, butresemble the circular arc predicted by the Cole-Cole model.

FIGS. 9A and 9B show the average amplitude and phase impedance spectra,respectively, of both normal intestine and intestine after 1.5 hours ofsevere ischemia, while FIG. 9C shows the normalized Nyquist plot of thenormal and ischemic intestinal tissue. Here, the ischemic tissue hassuffered moderate damage, and the spectra have become clearlydistinguishable B the ischemic tissue spectra have lost their circularshape and have taken on a sigmoidal shape with several inflectionpoints.

FIGS. 10A-10C show similar plots for normal intestines and intestinesafter two hours of severe ischemia. By now, the damage is even moresevere, and the spectra have become even more distorted.

FIGS. 11A-11C show the spectra of normal intestines and intestines afteran hour of ischemia followed by 1.5 hours of reperfusion. After an hourof ischemia, the tissue has suffered some damage. However, after beingreperfused, most of this damage has been reversed, and the spectra ofthe damaged tissue have largely regained their characteristic shape,although they are still somewhat abnormal and are still moderatelydistinguishable from the spectra of the normal tissue.

As should be appreciated, a plot or graph of the complex impedancespectrum of potentially damaged tissue versus the spectrum of normaltissue, e.g., as shown in FIGS. 8A-11C, can be used byappropriately-trained personnel to determine the level of damage due toischemia, by way of a visual comparison. Accordingly, the signalprocessing device 22 may be configured to graph or plot the spectrum forvisual analysis, accordingly the general guidelines given above, on ascreen or monitor, or by way of a print-out.

Alternatively, the signal processing device 22 can be configured toautomatically determine tissue damage, by way of the pattern recognitionsystem or other standard signal processing techniques, such asfiltering, or smoothing and extracting inflection points by analysis ofderivatives. Another alternative is the use of principal componentdecomposition or any other method of extracting a characteristic vectordescribing the shape of the spectrum. Such a characteristic vector canthen be analyzed by a classifying or pattern recognition algorithm toprovide a score in a predetermined tissue damage scale. Such analgorithm can use one of many standard techniques for classificationand/or pattern recognition, such as Bayesian statistics, neuralnetworks, fuzzy logic, statistical classifiers, expert systems, or anycombination of these. Further detail regarding a pattern recognitionsystem suitable for use or adaptation for use in the present inventioncan be found in U.S. Pat. No. 5,807,272 to Kun et al., previouslyincorporated by reference.

Although the preferred catheters have been illustrated as having Ag/AgClelectrodes, one of ordinary skill in the art will appreciate that othertypes of electrodes could be used instead without departing from thespirit and scope of the invention.

Although the electrodes and spacers of the fourth embodiment of thecatheter have been illustrated as having separate passageways andthrough-bores, one of ordinary skill in the art will appreciate that thepassageways and through-bores could be connected, i.e., they do not haveto be separate openings, as long as there is a space for the leads.

Since certain changes may be made in the above described impedancespectroscopy system and catheter for ischemic mucosal damage monitoringin hollow viscous organs, without departing from the spirit and scope ofthe invention herein involved, it is intended that all of the subjectmatter of the above description or shown in the accompanying drawingsshall be interpreted merely as examples illustrating the inventivemethod herein and shall not be construed as limiting the invention.

1. A method for monitoring mucosal damage in hollow viscous organscomprising the steps of: a. inserting a distal end of a catheter, with aplurality of spaced apart electrodes, into a hollow viscous organ, b.obtaining a complex impedance spectrum of the mucosa lining the hollowviscous organ by using an impedance spectrometer to electrically drivethe electrodes; and c. analyzing the complex impedance spectrum todetermine the extent to which the mucosa is damaged.
 2. The method ofclaim 1 wherein the step of analyzing the complex impedance spectrum ofthe mucosa comprises utilizing a pattern recognition system to determinethe extent to which the complex impedance spectrum of the mucosadeviates from that of normal tissue.
 3. The method of claim 1 whereinthe step of analyzing the complex impedance spectrum comprises: graphingthe complex impedance spectrum of the mucosa; and graphing a compleximpedance spectrum of normal tissue, wherein the graphed compleximpedance spectrum of the mucosa and the graphed complex impedancespectrum of normal tissue are normalized to facilitate a visualcomparison between the two by trained personnel.
 4. The method of claim1 wherein the step of analyzing the complex impedance spectrum comprisescross-referencing the complex impedance spectrum to anexperimentally-validated damage index scale that provides adetermination of the extent to which the mucosa is damaged.
 5. Themethod of claim 1 wherein the step of analyzing the complex impedancespectrum comprises the sub-steps of: i. utilizing a pattern recognitionsystem to determine the extent to which the complex impedance spectrumdeviates from that of normal tissue; and ii. generating a referencepoint on an experimentally-validated damage index scale, based on thedetermination of the extent to which the complex impedance spectrumdeviates from that of normal tissue, wherein the reference pointprovides a measure of mucosal damage.
 6. A method for monitoring damagein hollow viscous organs comprising the steps of: a. inserting a distalend of a catheter, with a plurality of spaced apart electrodes, into ahollow viscous organ, b. obtaining a complex impedance spectrum oftissue in the hollow viscous organ by using an impedance spectrometer toelectrically drive the electrodes; and c. analyzing the compleximpedance spectrum to determine the extent to which the tissue isdamaged.
 7. The method of claim 6 wherein the step of analyzing thecomplex impedance spectrum comprises applying a pattern matchingalgorithm to the complex impedance spectrum, wherein the output of thepattern matching algorithm is a reference point on anexperimentally-validated damage index scale, and the reference point,when cross-referenced to the scale, provides a determination of theextent to which the tissue is damaged.
 8. The method of claim 6 whereinthe step of analyzing the complex impedance spectrum comprises applyinga signal processing algorithm to the complex impedance spectrum, whereinthe output of the signal processing algorithm is a reference point on anexperimentally-validated damage index scale, and the reference point,when cross-referenced to the scale, provides a determination of theextent to which the tissue is damaged.
 9. The method of claim 6 whereinthe step of analyzing the complex impedance spectrum comprises graphingthe complex impedance spectrum of the tissue and graphing a compleximpedance spectrum of normal tissue, wherein the graph of the compleximpedance spectrum of the tissue and the graph of the complex impedancespectrum of normal tissue are both normalized to facilitate a visualcomparison between the two graphs.